Dataset Information

Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care.

ABSTRACT:

Objective

To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones).

Design

Open cohort study.

Setting

1243 general practices contributing data to the QResearch database in England.

Participants

469?688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015.

Exposures

Diabetes drugs (glitazones, gliptins, metformin, sulphonylureas, insulin, other) alone and in combination.

Main outcome measure

First recorded diagnoses of cardiovascular disease, heart failure, and all cause mortality recorded on the patients' primary care, mortality, or hospital record. Cox proportional hazards models were used to estimate hazard ratios for diabetes treatments, adjusting for potential confounders.

Results

During follow-up, 21?308 patients (4.5%) received prescriptions for glitazones and 32?533 (6.9%) received prescriptions for gliptins. Compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular disease; corresponding values for glitazones were significantly decreased risks of 23% for all cause mortality, 26% for heart failure, and 25% for cardiovascular disease. Compared with no current treatment, there were no significant associations between monotherapy with gliptins and risk of any complications. Dual treatment with gliptins and metformin was associated with a decreased risk of all three outcomes (reductions of 38% for heart failure, 33% for cardiovascular disease, and 48% for all cause mortality). Triple treatment with metformin, sulphonylureas, and gliptins was associated with a decreased risk of all three outcomes (reductions of 40% for heart failure, 30% for cardiovascular disease, and 51% for all cause mortality). Compared with no current treatment, monotherapy with glitazone was associated with a 50% decreased risk of heart failure, and dual treatment with glitazones and metformin was associated with a decreased risk of all three outcomes (reductions of 50% for heart failure, 54% for cardiovascular disease, and 45% for all cause mortality); dual treatment with glitazones and sulphonylureas was associated with risk reductions of 35% for heart failure and 25% for cardiovascular disease; triple treatment with metformin, sulphonylureas, and glitazones was associated with decreased risks of all three outcomes (reductions of 46% for heart failure, 41% for cardiovascular disease, and 56% for all cause mortality).

Conclusions

There are clinically important differences in risk of cardiovascular disease, heart failure, and all cause mortality between different diabetes drugs alone and in combination. Overall, use of gliptins or glitazones was associated with decreased risks of heart failure, cardiovascular disease, and all cause mortality compared with non-use of these drugs. These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, might have implications for prescribing of diabetes drugs.

SUBMITTER: Hippisley-Cox J

PROVIDER: S-EPMC4948032 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care.

Hippisley-Cox Julia J Coupland Carol C

BMJ (Clinical research ed.) 20160712

<h4>Objective</h4> To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones).<h4>Design</h4> Open cohort study.<h4>Setting</h4> 1243 general practices contributing data to the QResearch database in England.<h4>Participants</h4> 469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 Jan ...[more]

PMID: 27413012

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Project description:ObjectiveTo assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones).DesignOpen cohort study in primary care.Setting1243 practices contributing data to the QResearch database in England.Participants469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015.ExposuresHypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination.Main outcome measuresFirst recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders.Results21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94).ConclusionsWe have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.

Project description:BACKGROUND:Heart failure (HF) represents an accumulated burden of systemic vascular damage and is the fastest growing form of cardiovascular disease (CVD). Due to increasing HF-attributable mortality rates, we sought to assess the association of the new 2019 Pooled Cohort equations to Prevent Heart Failure (PCP-HF) risk score with CVD and all-cause mortality. METHODS:We linked data for 6333 black and white men and women aged 40-79?years, whom underwent electrocardiographic examination from the Third National Health and Nutrition Exam Survey, to National Death Index record matches. Sex- and race-specific PCP-HF risk scores were calculated using data on age, smoking, body mass index, systolic blood pressure, total cholesterol, HDL-cholesterol, fasting blood glucose, QRS complex duration, and antihypertensive and/or glucose-lowering medications. Cox regression estimated hazard ratios for the association of the PCP-HF risk score with CVD and all-cause mortality. RESULTS:Individuals were on average 54.9?years old (51.7% women, 25.4% black) and the median 10-year HF risk was 1.6% (Q1?=?0.5, Q3?=?4.8). There were 3178 deaths, 1116 from CVD, over a median follow-up time of 22.3?years. Black women had a higher 10-year HF risk compared to white women (2.1% vs. 1.1%; p?<?0.01), while no significant difference was observed in predicted HF risk between black men and white men (2.3% vs. 2.1%, p?=?0.16). A two-fold higher PCP-HF risk score was associated with a significant 58% (HR?=?1.58; 95% CI, 1.48-1.70; p?<?0.0001) and 38% (HR?=?1.38; 95% CI, 1.32-1.46; p?<?0.0001) greater risk of CVD and all-cause mortality, respectively. CONCLUSION:The PCP-HF risk score predicts CVD and all-cause mortality, in addition to the 10-year risk of incident HF among white and black men and women. These results underline the expanded utility of the PCP-HF risk score and suggest that its implementation in the clinical and population health settings may improve primary CVD prevention in the United States.

Project description:BackgroundUnderstanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment.MethodsWe investigated 14,373 participants (45.5% men) aged 45-84 from two large US prospective cohort studies with a median of 23 years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model.ResultsSeven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors. Individuals with the highest but decreasing LDL-C and borderline high and rising TG levels over time were at the highest risk than those in other groups with a 2.22-fold risk of CVD. Also, those with the highest and increased triglyceride levels over time, over optimal and decreasing LDL-C levels, and the lowest HDL-C profile had a nearly 1.84 times CVD risk. Even individuals in the multi-trajectory group with the highest HDL-C, optimal LDL-C, and optimal TG levels had a significant risk (HR, 1.45; 95% CI 1.02-2.08). Furthermore, only those with the highest HDL-C profile increased the risk of heart failure by 1.5-fold (95% CI 1.07-2.06).ConclusionsThe trajectories and risk of CVD identified in this study demonstrated that despite a decline in LDL-C over time, a significant amount of residual risk for CVD remains. These findings suggest the impact of the increasing trend of TG on CVD risk and emphasize the importance of assessing the lipid levels at each visit and undertaking potential interventions that lower triglyceride concentrations to reduce the residual risk of CVD, even among those with the optimal LDL-C level.

Dataset Information

Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care.

Objective

Design

Setting

Participants

Exposures

Main outcome measure

Results

Conclusions

Publications

Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care.

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